What is the prognostication and management plan for a 12x8x7 mm nodule in the central right upper lobe with positive Thyroid Transcription Factor-1 (TTF-1) and negative p40 on biopsy?

From the Guidelines

The 12x8x7 mm nodule in the central right upper lobe with positive TTF-1 and negative p40 on biopsy is highly suggestive of primary lung adenocarcinoma, and the next step should be complete staging with PET/CT scan and brain MRI to determine the extent of disease. According to the guidelines for management of incidental pulmonary nodules detected on CT images from the Fleischner Society 2017 1, for solitary solid noncalcified nodules larger than 8 mm in diameter, a 3-month follow-up, work-up with combined positron emission tomography (PET) and CT (PET/CT), tissue sampling, or a combination thereof may be appropriate.

Given the size of the nodule (12x8x7 mm) and its location in the central right upper lobe, along with the positive TTF-1 and negative p40 staining, which supports a diagnosis of lung adenocarcinoma 1, the approach should prioritize confirming the diagnosis and assessing the extent of the disease.

The following steps are recommended:

• Complete staging with PET/CT scan and brain MRI to determine the extent of disease.
• If the cancer is localized (stage I-II), surgical resection with lobectomy and mediastinal lymph node sampling would be the preferred treatment approach, offering the best chance for cure.
• For a nodule of this size, if surgery is not an option due to medical comorbidities, stereotactic body radiation therapy (SBRT) could be considered.
• If staging reveals locally advanced disease (stage III), a multidisciplinary approach with chemoradiation therapy would be recommended.
• For metastatic disease (stage IV), molecular testing for targetable mutations (EGFR, ALK, ROS1, BRAF, NTRK, MET, RET, HER2) and PD-L1 expression should guide therapy selection.

Prognosis depends heavily on stage at diagnosis, with 5-year survival rates ranging from approximately 70-90% for stage I to less than 10% for stage IV disease without targetable mutations. The management of patients with pulmonary nodules is best performed within the context of a multidisciplinary team, comprising radiologists, nuclear medicine specialists, surgeons, pulmonologists, and cancer specialists 1.

From the Research

Prognostication

• The patient has a 12x8x7 mm nodule in the central right upper lobe with positive TTF-1 and negative p40 on biopsy, which suggests lung adenocarcinoma 2.
• TTF-1 expression is associated with better survival in patients with lung adenocarcinoma, with a median overall survival of 18 months compared to 9 months for TTF-1 negative tumors 2.
• The presence of TTF-1 positivity is a favorable prognostic factor, exceeding the prognostic impact of Karnofsky performance status and receipt of first-line combination chemotherapy or targeted therapy 2.

Further Management Plan

• The patient's TTF-1 positive status suggests that they may benefit from targeted therapy or chemotherapy regimens that are effective in TTF-1 positive lung adenocarcinoma 2, 3.
• However, the optimal chemotherapy regimen for TTF-1 positive patients is not clearly defined, and pemetrexed-based chemotherapy may not be superior to other regimens 3.
• Further evaluation of the patient's tumor characteristics, such as EGFR mutation status, and consideration of other treatment options, such as targeted therapy or immunotherapy, may be necessary to determine the best course of treatment.
• The patient's negative p40 status suggests that they may not have squamous cell carcinoma, but further evaluation of the tumor's histology and molecular characteristics is necessary to confirm the diagnosis and guide treatment decisions.